ABSTRACT
INTRODUCTION: Various subtypes of severe acute respiratory syndrome coronavirus 2 and variations among immune systems in different ethnicities need to be considered to understand the outcomes of coronavirus disease 2019 (COVID-19). This study aimed to provide evidence for the association between the use of antidepressants and the severity of COVID-19. METHODS: We used the National Health Information Data-COVID database. Patients with one or more prescriptions of any antidepressant were selected as the exposure group. Detailed analyses were performed to determine the type of medication associated with the prognosis. RESULTS: The use of selective serotonin reuptake inhibitors (SSRIs) was associated with a lower risk of severe outcomes of COVID-19, whereas the use of tricyclic antidepressants (TCAs) increased the risk of poor prognosis of COVID-19. Detailed analyses showed that escitalopram was significantly associated with better clinical outcomes, and nortriptyline was linked to more severe COVID-19 outcomes. CONCLUSION: This study revealed an association between antidepressants and COVID-19 prognosis. SSRIs were significantly associated with a lower risk of severe outcomes, whereas TCAs were related to the poor prognosis of COVID-19.
Subject(s)
COVID-19 , Antidepressive Agents/adverse effects , Antidepressive Agents, Tricyclic/adverse effects , Humans , Prognosis , Selective Serotonin Reuptake Inhibitors/adverse effectsABSTRACT
Since the recent clinical approval of siRNA-based drugs and COVID-19 mRNA vaccines, the potential of RNA therapeutics for patient healthcare has become widely accepted. Lipid nanoparticles (LNPs) are currently the most advanced nanocarriers for RNA packaging and delivery. Nevertheless, the intracellular delivery efficiency of state-of-the-art LNPs remains relatively low and safety and immunogenicity concerns with synthetic lipid components persist, altogether rationalizing the exploration of alternative LNP compositions. In addition, there is an interest in exploiting LNP technology for simultaneous encapsulation of small molecule drugs and RNA in a single nanocarrier. Here, we describe how well-known tricyclic cationic amphiphilic drugs (CADs) can be repurposed as both structural and functional components of lipid-based NPs for mRNA formulation, further referred to as CADosomes. We demonstrate that selected CADs, such as tricyclic antidepressants and antihistamines, self-assemble with the widely-used helper lipid DOPE to form cationic lipid vesicles for subsequent mRNA complexation and delivery, without the need for prior lipophilic derivatization. Selected CADosomes enabled efficient mRNA delivery in various in vitro cell models, including easy-to-transfect cancer cells (e.g. human cervical carcinoma HeLa cell line) as well as hard-to-transfect primary cells (e.g. primary bovine corneal epithelial cells), outperforming commercially available cationic liposomes and state-of-the-art LNPs. In addition, using the antidepressant nortriptyline as a model compound, we show that CADs can maintain their pharmacological activity upon CADosome incorporation. Furthermore, in vivo proof-of-concept was obtained, demonstrating CADosome-mediated mRNA delivery in the corneal epithelial cells of rabbit eyes, which could pave the way for future applications in ophthalmology. Based on our results, the co-formulation of CADs, helper lipids and mRNA into lipid-based nanocarriers is proposed as a versatile and straightforward approach for the rational development of drug combination therapies.
Subject(s)
COVID-19 Drug Treatment , Nanoparticles , Animals , Antidepressive Agents, Tricyclic , Cations , Cattle , Drug Combinations , Drug Repositioning , HeLa Cells , Humans , Lipids/chemistry , Liposomes , Nanoparticles/chemistry , Nortriptyline , RNA, Messenger/genetics , RNA, Small Interfering/genetics , RabbitsABSTRACT
BACKGROUND: This study aims to provide 12-year nationwide epidemiology data to investigate the epidemiology and comorbidities of and therapeutic options for chronic fatigue syndrome (CFS) by analyzing the National Health Insurance Research Database. METHODS: 6306 patients identified as having CFS during the 2000-2012 period and 6306 controls (with similar distributions of age and sex) were analyzed. RESULT: The patients with CFS were predominantly female and aged 35-64 years in Taiwan and presented a higher proportion of depression, anxiety disorder, insomnia, Crohn's disease, ulcerative colitis, renal disease, type 2 diabetes, gout, dyslipidemia, rheumatoid arthritis, Sjogren syndrome, and herpes zoster. The use of selective serotonin receptor inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), Serotonin antagonist and reuptake inhibitors (SARIs), Tricyclic antidepressants (TCAs), benzodiazepine (BZD), Norepinephrine-dopamine reuptake inhibitors (NDRIs), muscle relaxants, analgesic drugs, psychotherapies, and exercise therapies was prescribed significantly more frequently in the CFS cohort than in the control group. CONCLUSION: This large national study shared the mainstream therapies of CFS in Taiwan, we noticed these treatments reported effective to relieve symptoms in previous studies. Furthermore, our findings indicate that clinicians should have a heightened awareness of the comorbidities of CFS, especially in psychiatric problems.